Depression is common in cancer patients. We investigated the effects of playing a serious game in breast cancer patients with mild to moderate depression using functional neuroimaging. Thirty-five participants were randomly assigned to the Game group and the Nongame group, and fifteen participants in each group completed the study protocol. Participants in the Game group were asked to play a serious game, "Hit the Cancer" (RAW HAND, Seoul, Korea), for at least 30 minutes/day, 5 days/week, for 3 weeks. Participants in the Nongame group received usual care. At baseline and follow-up, all participants were assessed with the Beck Depression Inventory (BDI), Beck Anxiety Inventory, Stress Response Inventory (SRI), and 3-Tesla resting-state functional magnetic resonance imaging. Changes in functional connectivity (FC) between the brain regions in the default mode network (DMN) and salience network (SN) were analyzed. After the intervention, BDI and SRI scores in the Game group greatly decreased compared with those in the Nongame group. In addition, compared with the Nongame group, the Game group showed decreased postintervention FC between the right posterior cingulate cortex (PCC) of the DMN and right insula of the SN. The improvement in BDI and SRI scores correlated with the decrease in FC between the right PCC and right insula. Selective attention training and repetitive stimulation of the insula by serious game play might cause normalization of the FC between the SN and DMN, thus improving depressive mood.

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